A 52-week open-label randomized trial found once-weekly semaglutide reduced LDL cholesterol and shifted lipoprotein subfractions toward a less atherogenic profile versus sitagliptin in obese type 2 diabetes. PICO summary and expert commentary.
Browsing: Therapeutics
Drug-class and individual-agent evidence: GLP-1 receptor agonists, SGLT2 inhibitors, and the major trials behind semaglutide, tirzepatide, and related therapies.
An RCT finds adding a ketogenic diet to dulaglutide improves glucose, lipids, and insulin resistance in type 2 diabetes. PICO summary and clinical expert commentary.
A Lancet phase 2 RCT finds once-weekly semaglutide 2.4 mg reduces heavy drinking days in alcohol use disorder with obesity. PICO summary and expert commentary for clinicians.
The DAPAHEART follow-up finds 4 years of dapagliflozin improves coronary flow reserve and reduces epicardial fat in type 2 diabetes. PICO summary and expert commentary.
The SCALE trial established liraglutide 3.0 mg as the first GLP-1 receptor agonist approved for chronic weight management, demonstrating a mean weight reduction of 8.0% versus 2.6% with placebo and a 79% reduction in progression from prediabetes to type 2 diabetes in a 160-week extension analysis, setting the clinical and regulatory template for GLP-1 receptor agonist obesity pharmacotherapy.
The SELECT trial demonstrated that semaglutide 2.4 mg reduces 3-point MACE by 20% in overweight or obese adults with pre-existing cardiovascular disease and no diabetes, becoming the first obesity pharmacotherapy trial to demonstrate a hard cardiovascular endpoint benefit and establishing GLP-1 receptor agonism as a cardiovascular intervention in non-diabetic obesity.
SURMOUNT-1 demonstrated that tirzepatide, a dual GIP/GLP-1 receptor agonist, produces dose-dependent mean weight reductions of 15.0–20.9% in adults with obesity without type 2 diabetes, with 57% of participants at the 15 mg dose losing 20% or more of body weight, setting a new pharmacological efficacy benchmark comparable in magnitude to bariatric surgery outcomes.
STEP 1 demonstrated that once-weekly semaglutide 2.4 mg produced a mean weight reduction of 14.9% compared with 2.4% with placebo in adults with obesity without type 2 diabetes, with a third of participants losing more than 20% of body weight, setting a new benchmark for pharmacological weight management and preceding the cardiovascular outcomes evidence from SELECT.
The REWIND trial demonstrated that dulaglutide reduces 3-point MACE in a broad type 2 diabetes population of which 69% had no established cardiovascular disease, with a significant 24% reduction in nonfatal stroke and consistent renal benefit, extending GLP-1 receptor agonist cardiovascular protection into a primary prevention context.
The SUSTAIN-6 trial demonstrated that once-weekly semaglutide reduced 3-point MACE by 26% in high-cardiovascular-risk type 2 diabetes, driven primarily by a significant 39% reduction in nonfatal stroke, while identifying a retinopathy complication signal attributable to rapid glucose lowering in patients with pre-existing retinopathy.